The retrograde intrabiliary injection technique has now been developed to the point where certain aspects of the absorption of marker compounds from the biliary tree can be studied. By assessing the changes in shape of the concentration-volume curve for the marker compounds recollected in bile, factors of bile flow and permeability changes can be assessed as they affect absorption of compounds from the biliary tree. Thus, treatment of rats with ethinylestradiol increases permeability of the biliary tree and decreases bile flow. Some bile salts produce choleresis while others produce choleresis and increase canalicular permeability. As we gather data to substantiate these preliminary findings, our approach will be broadened to include agents which affect the liver in different ways; cytochalasin, paraquat, amanita phalloides toxins, anabolic steroids, alpha-naphthylisothiocyanate, taurolithocholate to name a few. Will changes in canalicular membrane structure, canalicular permeability, biliary tree hyperplasia, bile duct obstruction, be detected and differentiated by use of our technique? A modified retrograde intrabiliary injection technique called segmented RII is being developed to study biliary tree permeability changes in a more facile manner. Evaluation of volume, pressure, time parameters for this technique will occupy our immediate effort. In order to understand some of the processes in the liver better, we believe techniques such as those being developed in this laboratory will add a new dimension to approaches already in use. BIBLIOGRAPHIC REFERENCES: Peterson, R.E. and Fujimoto, J.M.: Increased "bile duct-pancreatic fluid" flow in rats pretreated with carbon tetrachloride. Tox. Appl. Pharmacol. 35: 29-39, 1976. Peterson, R.E., Olson, J.R. and Fujimoto, J.M.: Measurement and alteration of the capacity of the distended biliary tree in the rat. Tox. Appl. Pharmacol. 36: 353-368, 1976.